Takahiro Oshima

Swainsonine reduces 5-fluorouracil tolerance in the multistage resistance of colorectal cancer cell lines.

BackgroundDrug resistance is a major problem in cancer chemotherapy. Acquisition of chemo-resistance not only reduces the effectiveness of drugs, but also promotes side effects and markedly reduces the patients quality of life. However, a number of resistance mechanisms have been reported and are thought to be the reason for the difficulties in solving drug-resistance problems.ResultTo investigate the mechanisms of drug resistance, a set of cell lines with different levels of sensitivity and possessing different mechanisms of resistance to 5-fluorouracil (5-FU) was established from a colorectal cancer cell line. The expression of thymidylate synthase, orotic acid phosphoribosyltransferase and dihydropyrimidine dehydrogenase, which are well known to be related to drug resistance, differed among these cell lines, indicating that these cell lines acquired different resistance mechanisms. However, swainsonine, an inhibitor of N-glycan biosynthesis, reduced 5-FU-tolerance in all resistant cells, whereas the sensitivity of the parental cells was unchanged. Further analysis of the N-glycan profiles of all cell lines showed partial inhibition of biosynthesis and no cytotoxicity at the swainsonine dosage tested.ConclusionThese observations suggest that N-linked oligosaccharides affect 5-FU resistance more widely than do drug-resistance related enzymes in colorectal cancer cells, and that the N-glycan could be a universal target for chemotherapy. Further, swainsonine may enhance the performance of chemotherapy by reducing tolerance.

Midline extraperitoneal approach for bilateral widespread retroperitoneal abscess originating from anorectal infection

Highlights • Retroperitoneal abscesses originating from anorectal infection are rare events.• Surgical drainage of widespread retroperitoneal abscesses might be challenging.• Midline extraperitoneal approach is a useful option for retroperitoneal abscesses.

Interferon-b Inhibits Liver Metastases from Murine Colon 26 Carcinoma and its Highly Metastatic Variant

PurposeThe antitumor effects of Interferon-β (IFN-β) are due to its direct inhibition of cell proliferation, immunostimulatory activity, and the inhibition of angiogenesis. We investigated the mechanism of the effects of IFN-β on a murine colon 26 cell line (CT 26) and its highly metastatic variant (L5).MethodsWe examined its inhibitory effects on cell proliferation in vitro and the development of liver metastases in vivo.ResultsThe proliferation of CT 26 in vitro was inhibited by IFN-β in a dose- and time-dependent manner. The number of metastases was reduced in mice inoculated with CT 26 (P < 0.01) and L5 (P < 0.01) on Day 14 after treatment with IFN-β. The median survival rate of the mice inoculated with L5 administered IFN-β every other day, or every day was higher than in the control group (P < 0.05). A dorsal air sac assay demonstrated that IFN-β inhibited angiogenesis in mice inoculated with CT 26, but the effects disappeared with aminoguanidine, an inducible nitric oxide synthase inhibitor.ConclusionThese results showed that IFN-β directly inhibits the proliferation of CT 26. In addition, the in vivo experiments suggested that IFN-β might effectively inhibit liver metastases.